The present invention relates to the field of devices to study the electrophysiology of nerve and muscle tissues, and in particular to a dynamically configurable clamp device used to measure and control nerve and muscle tissues.
Voltage clamp systems are typically used in neuroscience to study the electrophysiology of nerve and muscle tissues. The relationship between current and voltage across excitable membranes are time varying, nonlinear, and spatially distributive, yielding useful information. By clamping the membrane potential to a step function, the voltage clamp system momentarily achieves spatial coherence and voltage invariance. The current injected back into the cell for maintaining a constant membrane potential may be equated to the ionic current that induces an action potential. Further decomposition of the ionic current due to sodium, potassium, and calcium may be done by ionic substitutions in the bathing solution of the tissue.
The resistance of the microelectrode as well as the cellular membrane resistance is large; on the order of megaohms. Currents associated with ion flux across a cellular membrane are quite small; on the order of nanoamperes. A short duration impulse (in microseconds) of current is passed across the membrane to establish the specified voltage. There are oscillations however, inherent to the impulse response of the system that must abate before the voltage can be sampled. In order to measure the flow of ions across the cellular membrane, it is necessary to hold the voltage of the membrane fixed, or clamped. Typically, this is accomplished by two independent microelectrodes; one to measure the current, i.e., ion flow, and the other to serve as a feedback pathway to an analog amplifier to reinforce the voltage clamp.
Another example of a prior art voltage clamp includes a single-electrode as shown in FIG. 1. The single-electrode system of FIG. 1 includes an electrode 10 that is placed in contact with a neuron, a switch 12 that selectively couples the electrode 10 to either an input voltage amplifier 14 or an output current injection unit 16. The output of the voltage amplifier 14 and the input of the current injection unit 16 are coupled to an analog feedback control unit 18, which also receive a command voltage input.
In such a single-electrode voltage clamp, the membrane potential of a neuron measured by using an electrode may be the input to a feedback control circuit. The output current may be injected back to the neuron via the same electrode. Conventionally, the voltage measurement and current injection must be decoupled by a hardware based time-multiplexing technique. The switch is used to momentarily disconnect the input to the voltage amplifier during the current injection phase, thereby avoiding potential positive feedback from the current injection to the voltage measurement.
Single-electrode voltage clamps are also disclosed in U.S. Published Patent Application Publication No. 2005/0090865. The systems disclosed in this published patent application include a digital signal processor that permit the clamp to operate in any of voltage clamp mode, current clamp mode, or a dynamic clamp mode.
Such voltage clamps, however, require that the input to a voltage amplifier be momentarily disconnected via a switch to avoid direct positive feedback from the current injection to the voltage measurement when using a single input lead. Such switching therefore, limits sampling rates.
There is a need therefore, for a system that may provide voltage clamp sampling at relatively high sampling rates using single input leads.